Unraveling virulence determinants in extended-spectrum beta-lactamase-producing Escherichia coli from East Africa using whole-genome sequencing.

Escherichia coli significantly causes nosocomial infections and rampant spread of antimicrobial resistance (AMR). There is limited data on genomic characterization of extended-spectrum ß-lactamase (ESBL)-producing E. coli from African clinical settings. This hospital-based longitudinal study unraveled the genetic resistance elements in ESBL E. coli isolates from Uganda and Tanzania using whole-genome sequencing (WGS). A total of 142 ESBL multi-drug resistant E. coli bacterial isolates from both Tanzania and Uganda were sequenced and out of these, 36/57 (63.1%) and 67/85 (78.8%) originated from Uganda and Tanzania respectively. Mutations in RarD, yaaA and ybgl conferring resistances to chloramphenicol, peroxidase and quinolones were observed from Ugandan and Tanzanian isolates. We reported very high frequencies for blaCTX-M-15 with 11/18(61.1%), and blaCTX-M-27 with 12/23 (52.1%), blaTEM-1B with 13/23 (56.5%) of isolates originating from Uganda and Tanzania respectively all conferring resistance to Beta-lactam-penicillin inhibitors. We observed chloramphenicol resistance-conferring gene mdfA in 21/23 (91.3%) of Tanzanian isolates. Extraintestinal E. coli sequence type (ST) 131 accounted for 5/59 (8.4%) of Tanzanian isolates while enterotoxigenic E. coli ST656 was reported in 9/34 (26.4%) of Ugandan isolates. Virulence factors originating from Shigella dysenteriae Sd197 (gspC, gspD, gspE, gspF, gspG, gspF, gspH, gspI), Yersinia pestis CO92 (irp1, ybtU, ybtX, iucA), Salmonella enterica subsp. enterica serovar Typhimurium str. LT2 (csgF and csgG), and Pseudomonas aeruginosa PAO1 (flhA, fliG, fliM) were identified in these isolates. Overall, this study highlights a concerning prevalence and diversity of AMR-conferring elements shaping the genomic structure of multi-drug resistant E. coli in clinical settings in East Africa. It underscores the urgent need to strengthen infection-prevention controls and advocate for the routine use of WGS in national AMR surveillance and monitoring programs.Availability of WGS analysis pipeline: the rMAP source codes, installation, and implementation manual can free be accessed via https://github.com/GunzIvan28/rMAP .

Hand hygiene intervention to optimise soil-transmitted helminth infection control among primary school children: the Mikono Safi cluster randomised controlled trial in northwestern Tanzania.

BACKGROUND: Soil-transmitted helminth (STH) infections are highly prevalent in resource-limited countries. We assessed the effect of a combination intervention aiming to enhance handwashing with soap on STH reinfection following mass drug administration among primary school children in Kagera region, Northwestern Tanzania. METHODS: We conducted a cluster randomised trial in sixteen primary schools with known high STH prevalence. Schools were randomly assigned in a 1:1 ratio to either receive the intervention or continue with routine health education. The intervention included teacher-led classroom teaching, parental engagement sessions, environmental modifications and improved handwashing stations. The evaluation involved two cross-sectional surveys in a representative sample of students, with the end-line survey conducted 12 months after the baseline survey. The primary outcome was the combined prevalence of Ascaris lumbricoides and Trichuris trichiura infections at the end-line survey. Secondary outcomes included reported handwashing behaviour, the prevalence and intensity of individual STHs, and hand contamination with STH ova and coliform bacteria. End-line STH prevalence and intensity were adjusted for baseline differences of potential confounders. RESULTS: At the end-line survey, 3081 school children (1566 from intervention schools and 1515 from control schools) provided interview data and stool specimens. More school children in the intervention group reported the use of water and soap during handwashing compared to school children in the control group (58% vs. 35%; aOR=1.76, 95%CI 1.28-2.43, p=0.001). The combined prevalence of A. lumbricoides and T. trichiura infections was 39% in both trial arms (aOR = 1.19; 95%CI 0.74-1.91). The prevalence of A. lumbricoides was 15% in the intervention and 17% in the control arm (aOR =1.24, 95%CI 0.59-2.59) and that of T. trichiura was 31% in both arms (aOR=1.17, 95%CI 0.73-1.88). No significant differences were found for STH infection intensity in both the main study and the hand contamination sub-study. CONCLUSIONS: The intervention was effective in increasing reported handwashing behaviour at school, but failed to show a similar effect in the home. The intervention had no effect on STH infection, possibly due to infection in the home environment, other transmission routes such as contaminated water or food or limited changes in school children's handwashing behaviour. TRIAL REGISTRATION: The trial was registered on June 21, 2017, by the International Standard Randomised Controlled Trial Number ( ISRCTN45013173) .

The importance of Escherichia coli clonal complex 10 and ST131 among Tanzanian patients on antimicrobial resistance surveillance programs.

The objective of this study was to characterize antimicrobial resistance (AMR) of WHO priority 1 critical pathogen (extrapathogenic Escherichia coli (ExPEC), sequence types (STs), and ST131 clades from patients in Tanzania so as to guide specific antimicrobial therapies and preventive measures. A total of 143 ExPEC strains (128 from pregnant women with urinary tract infections and 15 from children with blood stream infections) were collected between March 2016 and October 2017. These were characterized into ST-fimH clones by a 7-single nucleotide polymorphism quantitative polymerase chain reaction (7-SNP qPCR) and gene sequencing, and to ST131 clades by multiplex PCR. The extended-spectrum beta-lactamases (ESBL) production was 16.1% (23/143), and was predominantly due to the blaCTX-M-15 (91.3%, n=21). ESBL production was significantly more among strains from children (53.3%) than pregnant women (11.7%) (OR (95%CI): 8.61 (2.73-27.15); p-value <0.001)). Approximately 61.5% (n=88) ExPEC were typed into their respective STs/CCs (87 by the 7-SNP qPCR and by an additional of one or two genes sequencing). The commonest STs/CCs among typeable strains were CC10 (28.4%, n=25), ST131 (18.2%, n=16), and ST38 (10.2%, n=9). The ST131 clades (C1 (4, 25.0%) and C2 (6, 37.5%)) were predominantly associated with fluoroquinolone resistance and ESBL production, respectively. Approximately 60.8% of ExPEC strains and all dominant clones were typed by the 7-SNP qPCR by additional sequencing. The multiplex clade PCR allowed linkage of the global clone ST131 with AMR phenotypes. These feasible and user-friendly molecular tools can be routinely used for surveillance programs in resource-limited settings.

Global health electives: Ethical engagement in building global health capacity.

Purpose: Little is known about the impact medical trainees undertaking global health electives (GHEs) have on host institutions and their communities in low-and middle-income countries. The goal of this study was to explore the relationship dynamics associated with GHEs as perceived by host stakeholders at three sites in sub-Saharan Africa.Method: This case-based interpretive phenomenological study examined stakeholder perspectives in Mwanza, Tanzania, and Mbarara and Rugazi, Uganda, where the University of Calgary, Alberta, Canada has long-standing institutional collaborations. Between September and November 2017, 33 host stakeholders participated in semi-structured interviews and 28 host stakeholders participated in focus group discussions. Participant experiences were analyzed using interpretive phenomenological techniques.Results: The findings revealed that, although GHEs are well-established and a common experience for host stakeholders, their perceptions about who visiting medical trainees (VMTs) are remains indistinct. Participants acknowledged that there are a variety of benefits to GHEs, but overall VMTs appear to benefit the most from this unique learning opportunity. Host stakeholders described significant challenges and burdens of GHEs and recommended ways in which GHEs could be improved.Conclusions: GHEs need to be designed to better embrace ethical engagement and reciprocity with host stakeholders to ensure equity in benefits and responsibilities.

Predictors of the extended-spectrum-beta lactamases producing Enterobacteriaceae neonatal sepsis at a tertiary hospital, Tanzania.

The study was conducted to establish predictors of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) neonatal sepsis and mortality in a tertiary hospital, Tanzania. Between July and December 2016, blood culture was performed in neonates with clinical features of sepsis and neonates/mothers/guardians were screened for ESBL colonization. Selected isolates underwent whole genome sequencing to investigate relatedness. Logistic regression analysis was performed to determine predictors for ESBL-PE associated neonatal sepsis and mortality. Neonatal ESBL-PE sepsis was detected in 32(10.5%) of the 304 neonates investigated. Neonatal ESBL-PE sepsis was independently predicted by admission at the Intensive care Unit and positive mother and neonate ESBL-PE colonization. Deaths occurred in 55(18.1%) of neonates. Neonates infected with ESBL-PE, admitted at ICU, increased age and those transferred from other centres had significantly high mortality rates. Gram-negative bacteria formed the majority (76%) of the isolates, of which 77% were ESBL-PE. Virulent Klebsiella pneumoniae ST45 carrying blaCTX-M-15 were commonly isolated from neonates. Klebsiella pneumoniae (ST45) were the predominant cause of ESBL-PE neonatal sepsis and mortality. Improved infection control and antibiotic stewardship are crucial in controlling the spread of resistant strains. Rapid diagnostic tests to detect ESBL-PE in low-income countries are needed to guide treatment and reduce ESBL-PE-associated mortality.

The magnitude and correlates of Parvovirus B19 infection among pregnant women attending antenatal clinics in Mwanza, Tanzania.

BACKGROUND: Human parvovirus B19 (B19) infection has been associated with congenital infection which may result into a number of the adverse pregnancy outcomes. The epidemiology and the magnitude of B19 infections among pregnant women have been poorly studied in developing countries. This study was done to establish preliminary information about the magnitude of B19 among pregnant women attending antenatal clinics in the city of Mwanza, Tanzania. METHODS: A cross-sectional study was conducted between December 2014 and June 2015 among 258 pregnant women attending two antenatal clinics representing rural and urban areas in the city of Mwanza. Socio-demographic data were collected using structured data collection tool. Specific B19 IgM and IgG antibodies were determined using indirect enzyme linked immunosorbent assay kits (DRG Instruments GmbH, Germany). Data were analyzed using STATA version 11 software. RESULTS: The median age of study participants was 21 IQR (19-25) years. Of 253 pregnant women; 116(44.96%), 109(42.25%) and 33(12.79%) were in the first, second and third trimester respectively. The majority 168(66.4%) of women were from urban areas. Of 253 pregnant women, the overall prevalence of IgM was 83(32.8%) while that of IgG was 142(55.0%) among 258 women tested. A total of 50(19.4%) women were positive for both IgG and IgM indicating true IgM positive. History of baby with low birth weight (OR: 10, 95% CI: 1.82-58.05, P = 0.01) was independent predictor of B19 IgG seropositivity and being at the third trimester was protective (OR: 0.38, 95% CI: 0.16-0.92, P = 0.03). The IgG titers were found to decrease significantly as gestational age increases (Spearman's rho = -0.2939, p = 0.0004) CONCLUSION: More than a half of pregnant women in Mwanza city are B19 IgG sero-positive with about one third of these being B19 IgM seropositive. Further studies to determine the impact of B19 infections among pregnant women and their newborns are recommended in developing countries.

Predictors of blaCTX-M-15 in varieties of Escherichia coli genotypes from humans in community settings in Mwanza, Tanzania.

BACKGROUND: Extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae commonly cause infections worldwide. Bla CTX-M-15 has been commonly detected in hospital isolates in Mwanza, Tanzania. Little is known regarding the faecal carriage of ESBL isolates and bla CTX-M-15 allele among humans in the community in developing countries. METHODS: A cross-sectional study involving 334 humans from the community settings in Mwanza City was conducted between June and September 2014. Stool specimens were collected and processed to detect ESBL producing enterobacteriaceae. ESBL isolates were confirmed using disc approximation method, commercial ESBL plates and VITEK-2 system. A polymerase chain reaction and sequencing based allele typing for CTX-M ESBL genes was performed to 42 confirmed ESBL isolates followed by whole genome sequence of 25 randomly selected isolates to detect phylogenetic groups, sequence types plasmid replicon types. RESULTS: Of 334 humans investigated, 55 (16.5 %) were found to carry ESBL-producing bacteria. Age, history of antibiotic use and history of admission were independent factors found to predict ESBL-carriage. The carriage rate of ESBL-producing Escherichia coli was significantly higher than that of Klebsiella pneumoniae (15.1 % vs. 3.8 %, p = 0.026). Of 42 ESBL isolates, 37 (88.1 %) were found to carry the bla CTX-M-15 allele. Other transferrable resistance genes were aac(6')Ib-cr, aac(3)-IIa, aac(3)-IId, aadA1, aadA5, strA, strB and qnrS1. Eight multi-locus sequence types (ST) were detected in 25 E. coli isolates subjected to genome sequencing. ST-131 was detected in 6 (24 %), ST-38 in 5 (20 %) and 5 (20 %) clonal complex - 10(ST-617, ST-44) of isolates. The pathogenic phylogenetic groups D and B2 were detected in 8/25 (32 %) and 6/25 (24 %) of isolates respectively. BlaCTX-M-15 was found to be located in multiple IncY and IncF plasmids while in 13/25(52 %) of cases it was chromosomally located. CONCLUSION: The overlap of multi-drug resistant bacteria and diversity of the genotypes carrying CTX-M-15 in the community and hospitals requires an overall approach that addresses social behaviour and activity, rationalization of the antibiotic stewardship policy and a deeper understanding of the ecological factors that lead to persistence and spread of such alleles.

Predictors of disease complications and treatment outcome among patients with chronic suppurative otitis media attending a tertiary hospital, Mwanza Tanzania.

BACKGROUND: Chronic suppurative otitis media (CSOM) is a major health problem in developing countries causing hearing loss and life threatening complications. Early and effective treatment based on the knowledge of causative micro-organisms and predictors of outcome are crucial in preventing these associated complications. This study was conducted to determine the predictors of CSOM complications, treatment outcome and antimicrobial susceptibility of pathogens, thus providing essential evidence to formulate a policy for management of CSOM. METHODS: This was a prospective hospital based cross sectional study involving 301 patients attending Ear Nose and Throat (ENT) clinics at Bugando Medical Centre (BMC) between October 2013 and March 2014. A standardized data collection tool was used to collect demographics and clinical characteristics of patients with CSOM. Ear swabs were collected using sterile cotton swabs and transported to the laboratory for culture and antibiotic susceptibility testing. RESULTS: Out of 301 patients with CSOM; 187 (62.1 %) had positive aerobic culture within 48 h of incubation. Disease complications and poor treatment outcome were observed in 114 (37.8 %, 95 % CI; 32.2-43.3) and 46 (15.3 %, 95 % CI; 11.2-19.3) respectively. On multivariate logistic regression analysis factors found independently to predict both disease complications and poor treatment outcome were otalgia, being infected by multi drug resistant bacteria and being HIV positive. Prolonged illness duration before seeking medical attention was also found to be associated with disease complications (OR 1.029, 95 % CI 1.007-1.05, p = 0.01). A total of 116 (61 %) of gram negative bacteria were isolated. Of 34 Staphylococcus aureus, 14 (41 %) were found to be methicillin resistant Staphylococcus aureus (MRSA) while of 116 g negative enteric bacteria, 49 (42 %) were extended spectrum beta lactamases producers (ESBL). CONCLUSIONS: Findings of this study suggest that positive HIV status, infection due to multidrug resistant pathogens and otalgia are significantly associated with disease complications and poor treatment outcome. Of great importance this study confirms that prolonged illness duration without seeking medical attention significantly predicts disease complications. Urgent preventive measures and laboratory guided early treatment are necessary to reduce complications associated with CSOM.

Comparison of antimicrobial resistance patterns of ESBL and non ESBL bacterial isolates among patients with secondary peritonitis at Bugando Medical Centre, Mwanza - Tanzania.

BACKGROUND: Secondary peritonitis is a common surgical emergence with deadly outcomes when not timely and promptly intervened. The emergence of Extended spectrum beta lactamase producing bacteria (ESBL) poses treatment challenge at Bugando Medical Centre (BMC); hence a need to evaluate the magnitude of ESBL so as to guide specific therapy. METHODS: This was a cross sectional study conducted at BMC from May 2014 to April 2015 involving patients with secondary peritonitis. A questionnaire was used to collect patients' information. Peritoneal aspirate sample was collected intra-operatively and processed using standard operating procedures to identify bacteria species and their susceptibility profiles. RESULTS: The study involved 97 patients with the median age (IQR) of 32 (21-47) years, males were 62 (63.9 %) and about 27 (27.8 %) patients had co-morbid illnesses. The prevalence of ESBL among patients with secondary peritonitis was 23.7 % (23/97). Of 53 gram negative Enterobacteriaceae isolated, 47.2 % (25/53) were ESBL producers, with predominance of Escherichia coli 7 (28.0 %) and Klebsiella spp 5 (20.0 %). The ESBL isolates exhibited more resistance rates to trimethoprim sulfamethoxazole and ciprofloxacin compared to non ESBL isolates 96.0 % versus 60.7 %, p value = 0.003 and 16.0 % versus 0.0 %, p value = 0.043 respectively). All isolates were sensitive to meropenem. CONCLUSIONS: The prevalence of ESBL among patients with secondary peritonitis at BMC is high; with more resistance rates among ESBL compared to non ESBL isolates. There is a need for strengthen ESBL surveillance in this setting so as to guide specific therapy.

Predominance of rotavirus G1[P8] genotype among under-five children with gastroenteritis in Mwanza, Tanzania.

We analyzed stool samples from underfives with gastroenteritis for rotavirus infection between January 2010 and June 2011. A total of 393 stool specimens were examined for rotavirus infection using enzyme-linked immunosorbent assay (ELISA). Hundred selected positive specimens were genotyped using multiplex polymerase chain reaction. Out of 393 underfives, 194 (49.4%) had rotavirus infection, with 96.9% of infected underfives being <2 years. Underfives infected with rotavirus had prolonged hospital stay than those without rotavirus infection (P = 0.0001). G1 was the most predominant G type (59%) followed by G8 (13%) while P[8] was the most predominant P type (25%). In single-type infection, common G-P combinations were G1P[8] (24%) and G1P[6] (17%). Common mixed infections were G1/G8 (16%) and P4/P8 (13%). G1 genotype is common among underfives with gastroenteritis in Mwanza. Diversity of genotypes causing gastroenteritis in Mwanza necessitates a continuous surveillance after the introduction of RotaRix® vaccine.

Developing a logic model for communication-based interventions on antimicrobial resistance (AMR).

The importance of communication in enhancing people's awareness and understanding of antimicrobial resistance (AMR) is consistently recognised in global and national action plans (NAPs). Despite this, there have been relatively few national AMR communication campaigns which use a structured approach to take account of the local context, encompass co-design with the target audience and use a logic model to help inform its design, implementation and evaluation. Designing a logic model for communication-based interventions can help map out the planning, resources, messaging, assumptions and intended outcomes of the campaign to maximise its impact, ensure it is fit for context and minimise any unintended consequences on individuals and society. Building on an AMR research project in Tanzania, Supporting the National Action Plan for AMR (SNAP-AMR), we co-designed the SNAP-AMR Logic Model with key stakeholders to implement AMR communication campaigns and related legacy materials to be employed in support of the Tanzanian NAP, but with broader relevance to a range of contexts. In developing the SNAP-AMR Logic Model, we reviewed relevant communication theories to create and target messages, and we considered behavioural change theories. We defined all key elements of the SNAP-AMR Logic Model as follows: (1) resources (inputs) required to enable the design and implementation of campaigns, e.g. funding, expertise and facilities; (2) activities, e.g. co-design of workshops (to define audience, content, messages and means of delivery), developing and testing of materials and data collection for evaluation purposes; (3) immediate deliverables (outputs) such as the production of legacy materials and toolkits; and (4) changes (outcomes) the campaigns aim to deliver, e.g. in social cognition and behaviours. The SNAP-AMR Logic Model efficiently captures all the elements required to design, deliver and evaluate AMR communication-based interventions, hence providing government and advocacy stakeholders with a valuable tool to implement their own campaigns. The model has potential to be rolled out to other countries with similar AMR socio-cultural, epidemiological and economic contexts.

External ocular surface bacterial isolates and their antimicrobial susceptibility patterns among pre-operative cataract patients at Mulago National Hospital in Kampala, Uganda.

BACKGROUND: Endophthalmitis is a severe complication of cataract surgery which leads to high ocular morbidity and visual loss even with antibiotic treatment. Bacterial ocular floras are the implicated causative agents. This study was undertaken to evaluate the external ocular surface bacterial isolates and their antimicrobial susceptibility patterns among pre-operative cataract patients at Mulago National Hospital. METHODS: This cross sectional study enrolled consecutively 131 patients scheduled for routine cataract surgery in the Department of Ophthalmology at Mulago National Hospital in Kampala, Uganda. Eyelid margin and conjunctival swabs were collected and processed using standard microbiological procedures to identify bacterial isolates and their respective antimicrobial susceptibility patterns. RESULTS: Of 131 patients involved (mean age 63.3 ± 14.5 years), 54.2% (71/131) were females. The eyelid margin and conjunctival samples were culture positive in 59.5% (78/138) and 45.8% (60/138) respectively. The most common organisms identified were Coagulase-negative Staphylococci (CoNS) [65.9% (91/138)] and Staphylococcus aureus [21.0% (29/138)]. CoNS showed the highest resistance to tetracycline (58.2%, 53/91) and erythromycin (38.5%, 35/91), whereas in S. aureus the resistance to tetracycline and erythromycin were 55.2% (16/29) and 31.0% (9/29) respectively. Methicillin resistant CoNS (MRS) and Methicillin resistance S. aureus (MRSA) were 31.9% (29/91) and 27.6% (8/29) respectively. There were low resistance rates for CoNS, S. aureus and other bacterial isolates to ciprofloxacin (11.1%-24.2%), gentamicin (5.6-31.0%), tobramycin (17.2% -25.3%) and vancomycin (0.0%). CONCLUSION: CoNS and S. aureus are the most common bacterial isolates found on the external ocular surface of the pre-operative cataract patients. Ciprofloxacin, gentamicin, tobramycin and vancomycin showed the lowest resistance rates to all bacterial isolates, therefore may be used to reduce bacteria load in the conjunctiva sac among cataract patients prior to surgery.

Patterns and outcomes of health-care associated infections in the medical wards at Bugando medical centre: a longitudinal cohort study.

BACKGROUND: The burden of healthcare associated infections (HCAIs) in low- and middle-income countries (LMICs) remains underestimated due to diagnostic complexity and lack of quality surveillance systems. We designed this study to determine clinical diagnosis, laboratory-confirmed, associated factors and risks of HCAIs. METHODS: This hospital-based longitudinal cohort study was conducted between March and June 2022 among adults (≥ 18 years) admitted in medical wards at BMC in Mwanza, Tanzania. Patients who were negative for HCAIs by clinical evaluations and laboratory investigations during admission were enrolled and followed-up until discharge or death. Clinical samples were collected from patients with clinical diagnosis of HCAIs for conventional culture and antimicrobial sensitivity testing. RESULTS: A total of 350 adult patients with a median [IQR] age of 54 [38-68] years were enrolled in the study. Males accounted for 54.6% (n = 191). The prevalence of clinically diagnosed HCAIs was 8.6% (30/350) of which 26.7% (8/30) had laboratory-confirmed HCAIs by a positive culture. Central-line-associated bloodstream infection (43.3%; 13/30) and catheter-associated urinary tract infection (36.7%; 11/30) were the most common HCAIs. Older age was the only factor associated with development of HCAIs [mean (± SD); [95%CI]: 58.9(± 12.5); [54.2-63.5] vs. 51.5(± 19.1); [49.4-53.6] years; p = 0.0391) and HCAIs increased the length of hospital stay [mean (± SD); [95%CI]: 13.8 (± 3.4); [12.5-15.1] vs. 4.5 (± 1.7); [4.3-4.7] days; p < 0.0001]. CONCLUSION: We observed a low prevalence of HCAIs among adult patients admitted to medical wards in our setting. Central-line-associated bloodstream infections and catheter-associated urinary tract infections are common HCAIs. Significantly, older patients are at higher risk of acquiring HCAIs as well as patients with HCAIs had long duration of hospital stays.

Spatial distribution of suspected and confirmed cholera cases in Mwanza City, Northern Tanzania.

Cholera, which is caused by Vibrio cholerae, persists as a devastating acute diarrheal disease. Despite availability of information on socio-cultural, agent and hosts risk factors, the disease continues to claim lives of people in Tanzania. The present study explores spatial patterns of cholera cases during a 2015-16 outbreak in Mwanza, Tanzania using a geographical information system (GIS) to identify concentrations of cholera cases. This cross-sectional study was conducted in Ilemela and Nyamagana Districts, Mwanza City. The two-phase data collection included: 1) retrospectively reviewing and capturing 852 suspected cholera cases from clinical files during the outbreak between August, 2015, and April, 2016, and 2) mapping of residence of suspected and confirmed cholera cases using global positioning systems (GPS). A majority of cholera patients were from Ilemela District (546, 64.1%), were males (506, 59.4%) and their median age was 27 (19-36) years. Of the 452 (55.1%) laboratory tests, 352 (77.9%) were confirmed to have Vibrio cholerae infection. Seven patients (0.80%) died. Cholera cases clustered in certain areas of Mwanza City. Sangabuye, Bugogwa and Igoma Wards had the largest number of confirmed cholera cases, while Luchelele Ward had no reported cholera cases. Concentrations may reflect health-seeking behavior as much as disease distribution. Topographical terrain, untreated water, physical and built environment, and health-seeking behaviors play a role in cholera epidemic in Mwanza City. The spatial analysis suggests patterns of health-seeking behavior more than patterns of disease. Maps similar to those generated in this study would be an important future resource for identifying an impending cholera outbreak in real-time to coordinate community members, community leaders and health personnel for guiding targeted education, outreach, and interventions.

"If You Do Not Take the Medicine and Complete the Dose It Could Cause You More Trouble": Bringing Awareness, Local Knowledge and Experience into Antimicrobial Stewardship in Tanzania.

Antimicrobial resistance (AMR) is a global health issue disproportionately affecting low- and middle-income countries. In Tanzania, multi-drug-resistant bacteria (MDR) are highly prevalent in clinical and community settings, inhibiting effective treatment and recovery from infection. The burden of AMR can be alleviated if antimicrobial stewardship (AMS) programs are coordinated and incorporate local knowledge and systemic factors. AMS includes the education of health providers to optimise antimicrobial use to improve patient outcomes while minimising AMR risks. For programmes to succeed, it is essential to understand not just the awareness of and receptiveness to AMR education, but also the opportunities and challenges facing health professionals. We conducted in-depth interviews (n = 44) with animal and human health providers in rural northern Tanzania in order to understand their experiences around AMR. In doing so, we aimed to assess the contextual factors surrounding their practices that might enable or impede the translation of knowledge into action. Specifically, we explored their motivations, training, understanding of infections and AMR, and constraints in daily practice. While providers were motivated in supporting their communities, clear issues emerged regarding training and understanding of AMR. Community health workers and retail drug dispensers exhibited the most variation in training. Inconsistencies in understandings of AMR and its drivers were apparent. Providers cited the actions of patients and other providers as contributing to AMR, perpetuating narratives of blame. Challenges related to AMR included infrastructural constraints, such as a lack of diagnostic testing. While health and AMR-specific training would be beneficial to address awareness, equally important, if not more critical, is tackling the challenges providers face in turning knowledge into action.

Identifying and addressing challenges to antimicrobial use surveillance in the human health sector in low- and middle-income countries: experiences and lessons learned from Tanzania and Uganda.

BACKGROUND: Antimicrobial resistance (AMR) is a global health security threat and is associated with increased morbidity and mortality. One of the key drivers of AMR is the inappropriate use of antibiotics. A key component of improving antibiotic use is conducting antimicrobial use (AMU) surveillance. METHODS: USAID Medicines Technologies and Pharmaceutical Services Program has supported the implementation of antimicrobial stewardship activities, including setting up systems for AMU surveillance in Tanzania and Uganda. Results from both countries have been previously published. However, additional implementation experience and lessons learned from addressing challenges to AMU surveillance have not been previously published and are the subject of this narrative article. RESULTS: The team identified challenges including poor quality data, low digitalization of tools, and inadequate resources including both financial and human resources. To address these gaps, the Program has supported the use of continuous quality improvement approaches addressing gaps in skills, providing tools, and developing guidelines to fill policy gaps in AMU surveillance. Recommendations to fill these gaps, based on the Potter and Brough systematic capacity building model have been proposed. CONCLUSIONS: Strengthening AMU surveillance through using a capacity-building approach will fill gaps and strengthen efforts for AMR control in both countries.

Molecular Characterizations of the Coagulase-Negative Staphylococci Species Causing Urinary Tract Infection in Tanzania: A Laboratory-Based Cross-Sectional Study.

BACKGROUND: There is a growing body of evidence on the potential involvement of coagulase-negative Staphylococci (CoNS) in causing urinary tract infections (UTIs). The aim of this study was to delineate virulence potential, antimicrobial resistance genes, and sequence types of CoNS isolated from patients with UTI symptoms and pyuria in Tanzania. METHODS: CoNS from patients with UTI symptoms and more than 125 leucocytes/µL were retrieved, subcultured, and whole-genome sequenced. RESULTS: Out of 65 CoNS isolates, 8 species of CoNS were identified; Staphylococcus haemolyticus, n = 27 (41.5%), and Staphylococcus epidermidis, n = 24 (36.9%), were predominant. The majority of S. haemolyticus were sequence type (ST) 30, with 8 new ST138-145 reported, while the majority of S. epidermidis were typed as ST490 with 7 new ST1184-1190 reported. Sixty isolates (92.3%) had either one or multiple antimicrobial resistance genes. The most frequently detected resistance genes were 53 (21%) dfrG, 32 (12.9%) blaZ, and 26 (10.5%) mecA genes conferring resistance to trimethoprim, penicillin, and methicillin, respectively. Out of 65 isolates, 59 (90.8%) had virulence genes associated with UTI, with a predominance of the icaC 47 (46.5%) and icaA 14 (13.9%) genes. Conclusion:S. haemolyticus and S. epidermidis harboring icaC, dfrG, blaZ, and mecA genes were the predominant CoNS causing UTI in Tanzania. Laboratories should carefully interpret the significant bacteriuria due to CoNS in relation to UTI symptoms and pyuria before labeling them as contaminants. Follow-up studies to document the outcome of the treated patients is needed to add more evidence that CoNS are UTI pathogens.

The hospital environment versus carriage: transmission pathways for third-generation cephalosporin-resistant bacteria in blood in neonates in a low-resource country healthcare setting.

Neonatal bloodstream infections (BSI) can lead to sepsis, with high morbidity and mortality, particularly in low-income settings. The high prevalence of third-generation cephalosporin-resistant organisms (3GC-RO) complicates the management of BSI. Whether BSI is linked to carriage of 3GC-RO, or to acquisition from the hospital environment is important for infection prevention and control, but the relationship remains unclear, especially in low-income settings. At a tertiary hospital in Mwanza, Tanzania, we screened neonatal blood and rectal samples from 200 neonates, and 400 (hospital) environmental samples. We used logistic regression to identify risk factors, and Kolmogorov-Smirnov tests and randomisation analyses to compare distributions of species and resistance patterns to assess potential routes of transmission. We found that BSIs caused by 3GC-RO were frequent (of 59 cases of BSI, 55 were caused by 3GC-RO), as was carriage of 3GC-RO, particularly Escherichia coli, Klebsiella pneumoniae, and Acinetobacter species. In the 28 infants with both a carriage and blood isolate, there were more (4 of 28) isolate pairs of the same species and susceptibility profile than expected by chance (p < 0.05), but most pairs were discordant (24 of 28). Logistic regression models found no association between BSI and carriage with either 3GC-RO or only 3GC-R K. pneumoniae. These analyses suggest that carriage of 3GC-RO is not a major driver of BSI caused by 3GC-RO in this setting. Comparison with environmental isolates showed very similar distributions of species and resistance patterns in the carriage, BSI, and the environment. These similar distributions, a high frequency of Acinetobacter spp. isolations, the lack of strong association between carriage and BSI, together with the high proportion of 3GC-RO in BSI all suggest that these neonates acquire multidrug-resistant carriage and blood isolates directly from the hospital environment.

Urinary Tract Infections and Associated Factors among Patients with Indwelling Urinary Catheters Attending Bugando Medical Centre a Tertiary Hospital in Northwestern Tanzania.

Complications of indwelling urinary catheterization (IUC) are associated with significant morbidity and mortality, thus affecting patient's well-being. Understanding the magnitude and factors associated with complications is crucial in designing appropriate preventive strategies. A cross-sectional study was conducted at Bugando Medical Centre, involving patients with long-term and short-term IUC from December 2016 to September 2017. The data were analyzed by STATA 13.0. Catheter-associated urinary tract infection (CA-UTI) was the leading (56.8%; 250/440) complication among patients with IUC. Gram-negative bacteria were predominantly isolated (98.1%, 252/257), whereas E. coli (30.7%, 79/257) and Klebsiella spp. (29.6%, 76/257) were the leading pathogens. CA-UTI was significantly higher among out-patients than in-patients (82.2% v 35.3%, p < 0.001). Older age (OR: 1.3, (95%CI: 1.1-1.5), p < 0.001), level of education (OR: 1.8, (95%CI: 1.1-3.1), p = 0.029) and catheter duration of ≥6 weeks (OR: 2.43, (95%CI: 1.1-5.5), p = 0.031) independently predicted CA-UTI among outpatients, while female gender (OR: 2.1, (95%CI: 1.2-3.7), p = 0.014), catheter bags not freely hanging (OR: 0.4, (95%CI: 0.2-0.7), p = 0.002) and residing outside Mwanza region (OR: 0.4, (95%CI: 0.2-0.6), p < 0.001) predicted CA-UTI among in-patients. CA-UTI is the common complication among patients with IUC, significantly higher in out-patients than in-patients. We recommend involving patients and carers in infection prevention and control measures in out-patients living with IUC.

Predominance of Other Pathogenic Bacteria among Presumptive Tuberculosis Cases Attending Tuberculosis Clinics in Mwanza, Tanzania: A Cross-Sectional Laboratory-Based Study.

This study was designed to determine the prevalence and co-infection of Mycobacterium tuberculosis and other pathogenic bacteria among presumptive cases of tuberculosis (TB) at selected hospitals in Mwanza, Tanzania. GeneXpert and conventional bacteriological culture and sensitivity were used for the detection of TB and other pathogenic bacteria, respectively. STATA version 13.0 was used for data analysis. The median (IQR) age of participants was 33 (19−51) years with males forming more than half (i.e., 59% (158/264)) of the participants. Microscopically, 29.5% (78/264) of the patients had polymorphonuclear leucocytes in the sputum samples. Approximately 7.2% (19/264), 16.3% (43/264), and 1.1% (3/264) of participants had TB, other pathogenic bacteria, and co-infections, respectively. One sample had growth of two other bacteria, resulting in a total of 44 isolated bacteria with the predominance of Gram-negative bacteria at 75.0% (33/44). The predominant species isolated was the Klebsiella pneumoniae complex at 52.3% (23/44). Overall, 27.3% (9/33) of GNB were resistant to third-generation cephalosporins, while Gram-positive bacteria were more resistant to erythromycin at 63.6% (7/11). Good quality sputa had a significantly higher yield of pathogenic bacteria than poor quality sputa (37.2% vs. 7.5%, p < 0.001). Presumptive TB cases were predominantly infected with other pathogenic bacteria than M. tuberculosis. Therefore, other pathogenic bacteria should be considered when attending presumptive TB cases to ensure favorable treatment outcomes.